Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain cancer with median survival of less than two years, even after aggressive treatment. Among the many challenges in treating patients with this devastating disease is differentiation of radiation induced change, often termed “radiation necrosis” (RN) from true tumor recurrence. Though recurrent GBM and RN have markedly different treatments and outcomes, they are so difficult to differentiate on MRI that new radiologic grading criterion had to be established for assessing progression in clinical trials. While numerous radiological approaches to distinguish the two have been proposed, no FDA approved technique has demonstrated efficacy in this regard and thus many patients undergo biopsy to distinguish these two possibilities. The rate of radiological uncertainty has recently been reported to be as high as ˜15% in a recent NCI-funded clinical trial. This diagnostic conundrum is expected to become even more common as immunotherapeutic treatments for GBM increase, as the immune response is also known to induce contrast enhancing lesions which are difficult to differentiate from tumor recurrence and new radiological grading schemes have been proposed and incorporated into clinical trials.